User-friendly prognostic model for rectal neuroendocrine tumours: In the era of precision management

In this letter,we explore into the potential role of the recent study by Zeng et al.Rectal neuroendocrine tumours(rNETs)are rare,originate from peptidergic neurons and neuroendocrine cells,and express corresponding markers.Although most rNETs patients have a favourable prognosis,the median survival period significantly decreases when high-risk factors,such as larger tumours,poorer differentiation,and lymph node metastasis exist,are present.Clinical prediction models play a vital role in guiding diagnosis and prognosis in health care,but their complex calculation formulae limit clinical use.Moreover,the prognostic models that have been developed for rNETs to date still have several limitations,such as insufficient sample sizes and the lack of external validation.A high-quality prognostic model for rNETs would guide treatment and follow-up,enabling the precise formulation of individual patient treatment and follow-up plans.The future development of models for rNETs should involve closer collab-oration with statistical experts,which would allow the construction of clinical prediction models to be standardized and robust,accurate,and highly general-izable prediction models to be created,ultimately achieving the goal of precision medicine.

Association of KRAS Gene and microRNA-124-3p in Sporadic Colorectal Tumours

Aim: To reveal the exonic and 3’UTR sequences of KRAS, TP53, APC, BRAF, PIK3CA genes in sporadic colorectal tumors and to investigate the clinical relevance of 3’UTR variations in miRNA profiles. Methods: In the study, the exonic and 3’UTR sequences of five genes in 12 sporadic colorectal tumors were extracted by next generation sequencing. In tumors with variation in the 3’UTR region, the changes caused by the variation in the miRNA binding profile were detected. The expression profile of these miRNAs in colorectal and other solid tumors compared to normal tissue was determined. Pathway analysis was performed to determine which signaling pathways miRNAs affect. Results: Case-10 in our study was wild type KRAS and received cetuximab treatment and developed drug resistance. In this case, it was concluded that the expression of KRAS increased and tumorigenesis progressed due to miRNAs that do not bind to this region due to variations in the 3’UTR region. Among these miRNAs, hsa-miR-124-3p was found to have decreased expression in colorectal tumors and to be associated with the ECM-receptor interaction pathway. Conclusion: Variations in the 3’UTR regions of genes critical in the process of carsinogenesis are associated with drug resistance and the process of tumorigenesis.

Clinical features and prognostic factors of duodenal neuroendocrine tumours:A comparative study of ampullary and nonampullary regions

BACKGROUND Duodenal neuroendocrine tumours(DNETs)are rare neoplasms.However,the incidence of DNETs has been increasing in recent years,especially as an incidental finding during endoscopic studies.Regrettably,there is no consensus regarding the ideal treatment of DNETs.Even there are few studies on the clinical features and survival analysis of DNETs.AIM To analyze the clinical characteristics and prognostic factors of patients with duodenal neuroendocrine tumours.METHODS The clinical data of DNETs diagnosed in the First Affiliated Hospital of Air Force Military Medical University from June 2011 to July 2022 were collected.Neuroen-docrine tumours located in the ampulla area of the duodenum were divided into the ampullary region group;neuroendocrine tumours in any part of the duo-denum outside the ampullary area were divided into the nonampullary region group.Using a retrospective study,the clinical characteristics of the two groups and risk factors affecting the survival of DNET patients were analysed.RESULTS Twenty-nine DNET patients were screened.The male to female ratio was 1:1.9,and females comprised the majority.The ampullary region group accounted for 24.1%(7/29),while the nonampullary region group accounted for 75.9%(22/29).When diagnosed,the clinical symptoms of the ampullary region group were mainly abdominal pain(85.7%),while those of the nonampullary region groups were mainly abdominal distension(59.1%).There were differences in the composition of staging of tumours between the two groups(Fisher's exact probability method,P=0.001),with nonampullary stage II tumours(68.2%)being the main stage(P<0.05).After the diagnosis of DNETs,the survival rate of the ampullary region group was 14.3%(1/7),which was lower than that of 72.7%(16/22)in the nonampullary region group(Fisher's exact probability method,P=0.011).The survival time of the ampullary region group was shorter than that of the nonampullary region group(P<0.000).The median survival time of the ampullary region group was 10.0 months and that of the nonampullary region group was 451.0 months.Multivariate analysis showed that tumours in the ampulla region and no surgical treatment after diagnosis were independent risk factors for the survival of DNET patients(HR=0.029,95%CI 0.004-0.199,P<0.000;HR=12.609,95%CI:2.889-55.037,P=0.001).Further analysis of nonampullary DNET patients showed that the survival time of patients with a tumour diameter<2 cm was longer than that of patients with a tumour diameter≥2 cm(t=7.243,P=0.048).As of follow-up,6 patients who died of nonampullary DNETs had a tumour diameter that was≥2 cm,and 3 patients in stage IV had liver metastasis.Patients with a tumour diameter<2 cm underwent surgical treatment,and all survived after surgery.CONCLUSION Surgical treatment is a protective factor for prolonging the survival of DNET patients.Compared to DNETs in the ampullary region,patients in the nonampullary region group had a longer survival period.The liver is the organ most susceptible to distant metastasis of nonampullary DNETs.

A deep learning fusion model for accurate classification of brain tumours in Magnetic Resonance images

Detecting brain tumours is complex due to the natural variation in their location, shape, and intensity in images. While having accurate detection and segmentation of brain tumours would be beneficial, current methods still need to solve this problem despite the numerous available approaches. Precise analysis of Magnetic Resonance Imaging (MRI) is crucial for detecting, segmenting, and classifying brain tumours in medical diagnostics. Magnetic Resonance Imaging is a vital component in medical diagnosis, and it requires precise, efficient, careful, efficient, and reliable image analysis techniques. The authors developed a Deep Learning (DL) fusion model to classify brain tumours reliably. Deep Learning models require large amounts of training data to achieve good results, so the researchers utilised data augmentation techniques to increase the dataset size for training models. VGG16, ResNet50, and convolutional deep belief networks networks extracted deep features from MRI images. Softmax was used as the classifier, and the training set was supplemented with intentionally created MRI images of brain tumours in addition to the genuine ones. The features of two DL models were combined in the proposed model to generate a fusion model, which significantly increased classification accuracy. An openly accessible dataset from the internet was used to test the model's performance, and the experimental results showed that the proposed fusion model achieved a classification accuracy of 98.98%. Finally, the results were compared with existing methods, and the proposed model outperformed them significantly.

The Value of MRI and CT in the Diagnosis of Retroperitoneal Tumours

Objective:This study aimed to investigate the effectiveness and value of MRI and CT in the diagnosis of retroperitoneal tumours.Methods:60 patients with retroperitoneal tumours admitted to our hospital between July 2022 and March 2023 were selected as the study subjects.All of them received MRI and CT examinations.The detection of the two examination methods was compared and analyzed using the pathological findings as the standard.Results:The detection rate of MRI(58/60,96.67%)was significantly higher than that of CT(50/60,83.33%),and the difference was significant(P=0.015<0.05).Conclusion:Both MRI and CT have important application values in the diagnosis of retroperitoneal tumours.MRI has advantages in observing soft tissue structures,nerve tissues,etc.,and can provide more detailed anatomical structure information,which can help differentiate the retroperitoneal tumours and locate them accurately.CT,on the other hand,has unique advantages in observing the skeletal structure and the density of certain tumours,etc.It can quickly obtain comprehensive imaging information,which helps to determine the extent and invasion of the tumour.

Primary epithelial tumours of the appendix in a black population:A review of cases

AIM： To determine the and clinical features of prevalence, histologic types primary epithelial tumours of the vermiform appendix in a predominantly black population.METHODS： All cases of primary tumours of the appendix identified by review of the histopathology records at the University of the West Indies between January 1987 and June 2007 were selected. Relevant pathologic and clinical data were extracted with supplementation from patient charts where available. Non-epithelial tumours were excluded. The total number of appendectomy specimens over the period was also ascertained.RESULTS： Forty-two primary epithelial tumours were identified out of 6 824 appendectomies yielding a prevalence rate of approximately 0.62%. Welldifferentiated neuroendocrine cell tumours （carcinoids, 47.6%） and benign non-endocrine cell tumours （adenomas, 45.2%） were most common with nearly equal frequency. The median age was 43 years, with no sex predilection. Carcinoid tumours occurred in younger patients （mean age 32 years）, with a male-to-female ratio of 1.2：1. A clinical diagnosis of acute appendicitis was the most common reason for appendectomy （57.1%） and was histologically confirmed in 75% （18 of 24） of cases. In total, 16.7% of cases were diagnosed after incidental appendectomy.CONCLUSION： Appendiceal epithelial tumours are rare in our experience, and are represented principally by carcinoid turnours and adenornas. Carcinoid tumours occurred in younger patients but were slightly more common in men than women. Tumours were not suspected clinically and were diagnosed incidentally in specimens submitted for acute appendicitis supporting the need for histological evaluation in all resection specimens.

Primary vascular tumours of the kidney

Primary vascular tumours of the kidney are rare and may pose diagnostic difficulties because of their similar clinical,morphological,and immunohistochemical features.This article summarizes the clinical and pathological features of primary renal angiosarcoma and anastomosing haemangioma of the kidney including epidemiology,genetics,and prognosis.Renal anastomosing haemangiomas are benign neoplasms characterized by anastomosing capillary-sized vascular channels.These tumours are rare,with about 75 cases reported in the literature.Most anastomosing haemangiomas are found incidentally on ultrasound,computed tomography,or magnetic resonance imaging.Common symptoms include abdominal pain,haematuria,and abdominal mass.Renal anastomosing haemangiomas are characterized by recurrent mutations in GNAQ and GNA14 genes.The prognosis of anastomosing haemangioma is excellent.Primary renal angiosarcomas are malignant tumours showing endothelial differentiation.To date,76 cases have been described in the literature.Primary renal angiosarcomas are frequently symptomatic.The clinical features of renal angiosarcomas are similar to those of renal anastomosing haemangiomas,including abdominal pain,haematuria,and abdominal mass.Angiogenesis-related genes and vascular-specific receptor tyrosine kinases such as KDR,TIE1,SNRK,TEK,and FLT1 are upregulated in angiosarcomas.Primary renal angiosarcomas are highly aggressive neoplasms with a poor prognosis despite surgical treatment,chemotherapy,radiotherapy,or targeted therapy.

Clinicopathological characteristics and prognosis of 77 cases with type 3 gastric neuroendocrine tumours

BACKGROUND For the rarity of type 3 gastric neuroendocrine tumours(g-NETs),their clinicopathological characteristics and prognosis are not well illustrated.AIM To describe the clinicopathological features and outcome of type 3 g-NETs in the Chinese population.METHODS Based on the 2019 WHO pathological classification,the clinicopathological characteristics and prognosis of patients with type 3 g-NETs in China were retrospectively analysed.RESULTS A total of 77 patients(55.8%of females)with type 3 g-NETs were analysed,with a median age of 48 years(range:28-79 years).The tumours were mainly located in the gastric fundus/body(83.1%)and were mostly solitary(83.1%),with a median size of 1.5 cm(0.8-3.5 cm).Of these,there were 37 G1 tumours(48.1%),31 G2(40.3%),and 9 G3(11.7%).Ten(13.0%)and 24(31.2%)patients had lymph node and distant metastasis,respectively.In addition,type 3 g-NETs were heterogeneous.Compared with G1 NETs,G2 NETs had a higher lymph node metastasis rate,and G3 NETs had a higher distant metastasis rate.G1 and G2 NETs with stage I/II disease(33/68)received endoscopic treatment,and no tumour recurrence or tumour-related death was observed within a median follow-up time of 36 mo.Grade and distant metastasis were identified to be independent risk factors for prognosis in multivariable analysis.CONCLUSION Type 3 g-NETs are obviously heterogeneous,and the updated WHO 2019 pathological classification may be used to effectively evaluate their biological behaviors and prognosis.Also,endoscopic treatment should be considered for small(<2 cm),low grade,superficial tumours.

Health-related quality of life, anxiety, depression and impulsivity in patients with advanced gastroenteropancreatic neuroendocrine tumours

AIM To compare health-related quality of life(HRQoL),anxiety, depression, and impulsivity scores in patients with and without carcinoid syndrome(CS), and correlated them with serum 5-hydroxyindoleacetic acid(5-HIAA) levels.METHODS Patients with advanced gastroenteropancreatic neuroendocrine tumours(GEPNET), with and without CS completed HRQoL QLQ-C30 and QLQ-GI.NET21, Hospital Anxiety and Depression Scale(HADS) and Barratt Impulsivity Scale(BIS) questionnaires. Twosample Wilcoxon test was applied to assess differences in serum 5-HIAA levels, two-sample Mann-Whitney U test for HRQoL and BIS, and proportion test for HADS, between those with and without CS.RESULTS Fifty patients were included; 25 each with and without CS. Median 5-HIAA in patients with and without CS was 367 nmol/L and 86 nmol/L, respectively(P = 0.003). Scores related to endocrine symptoms were significantly higher amongst patients with CS(P = 0.04) and scores for disease-related worries approached significance in the group without CS, but no other statistically-significant differences were reported between patients with and without CS in responses on QLQ-C30 or QLQ-GI.NET21. Fifteen patients(26%) scored ≥ 8/21 on anxiety scale, and 6(12%) scored ≥ 8/21 on depression scale. There was no difference in median 5-HIAA between those scoring < or ≥ 8/21 on anxiety scale(P = 0.53). There were no statistically significant differences between groups in first or second-order factors(BIS) or total sum(P = 0.23).CONCLUSION Excepting endocrine symptoms, there were no significant differences in HRQoL, anxiety, depression or impulsivity between patients with advanced GEPNET, with or without CS. Over one quarter of patients had high anxiety scores, unrelated to peripheral serotonin metabolism.

Prognostic importance of lymph node yield after curative resection of gastroenteropancreatic neuroendocrine tumours

BACKGROUND The prognostic significance of lymph nodes(LNs)metastases and the optimum number of LN yield in gastroenteropancreatic neuroendocrine tumours(GEP NETs)undergoing curative resection is still debatable.Many studies have demonstrated that cure rate for patients with GEP NETs can be improved by the resection of the primary tumour and regional lymphadenectomy AIM To evaluate the effect of lymph node(LN)status and yield on relapse-free survival(RFS)and overall survival(OS)in patients with resected GEP NETs.METHODS Data on patients who underwent curative resection for GEP NETs between January 2002 and March 2017 were analysed retrospectively.Grade 3 tumours(Ki67>20%)were excluded.Univariate Cox proportional hazard models were computed for RFS and OS and assessed alongside cut-point analysis to distinguish a suitable binary categorisation of total LNs retrieved associated with RFS.RESULTS A total of 217 patients were included in the study.The median age was 59 years(21-97 years)and 51%(n=111)were male.Primary tumour sites were small bowel(42%),pancreas(25%),appendix(18%),rectum(7%),colon(3%),gastric(2%),others(2%).Median follow up times for all patients were 41 mo(95%CI:36-51)and 71 mo(95%CI:63–76)for RFS and OS respectively;50 relapses and 35 deaths were reported.LNs were retrieved in 151 patients.Eight or more LNs were harvested in 106 patients and LN positivity reported in 114 patients.Three or more positive LNs were detected in 62 cases.The result of univariate analysis suggested perineural invasion(P=0.0023),LN positivity(P=0.033),LN retrieval of≥8(P=0.047)and localisation(P=0.0049)have a statistically significant association with shorter RFS,but there was no effect of LN ratio on RFS:P=0.1 or OS:P=0.75.Tumour necrosis(P=0.021)and perineural invasion(P=0.016)were the only two variables significantly associated with worse OS.In the final multivariable analysis,localisation(pancreas HR=27.33,P=0.006,small bowel HR=32.44,P=0.005),and retrieval of≥8 LNs(HR=2.7,P=0.036)were independent prognostic factors for worse RFS.CONCLUSION An outcome-oriented approach to cut-point analysis can suggest a minimum number of adequate LNs to be harvested in patients with GEP NETs undergoing curative surgery.Removal of≥8 LNs is associated with increased risk of relapse,which could be due to high rates of LN positivity at the time of surgery.Given that localisation had a significant association with RFS,a prospective multicentre study is warranted with a clear direction on recommended surgical practice and follow-up guidance for GEP NETs.

Quality of life in patients with gastroenteropancreatic tumours: A systematic literature review

BACKGROUND Gastroenteropancreatic neuroendocrine tumours(GEP-NETs)are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract(GINETs)or the pancreas(P-NETs).They are relatively uncommon,accounting for 2%of all gastrointestinal malignancies.The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy,biological therapies,and peptide receptor radionuclide therapy.Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease.Health-related quality of life(HRQoL)is increasingly important as a concept reflecting the patients’perspective in conjunction with the disease presentation,severity and treatment.AIM To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019.METHODS The PRISMA guiding principles were applied.MEDLINE,Embase and the Cochrane library were searched.Data extracted from the publications included type of study,patient population data(mid-gut/hind-gut/GI-NET/P-NET),sample size,intervention/comparators,HRQoL instruments,average and data spread of overall and sub-scores,and follow-up time for data collection.RESULTS Forty-three publications met the inclusion criteria.The heterogeneous nature of the different study populations was evident;the percentage of female participants ranged between 30%-60%,whilst average age ranged from 53.8 to 67.0 years.Eight studies investigated GI-NET patients only,six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour.The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30(n=28)with consistent results across studies;the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies.A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms.The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients;it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients’HRQoL.CONCLUSION HRQoL instruments offer a means to monitor patients’general disease condition,disease progression and their physical and mental well-being.Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack,however,validation and a defined minimal clinical important difference specifically for GINET and P-NET patients.

Tunneled biopsy is an underutilised,simple,safe and efficient method for tissue acquisition from subepithelial tumours

BACKGROUND Tissue acquisition from subepithelial lesions is often attempted by endoscopic ultrasound(EUS)-sampling as conventional endoscopic biopsy usually fails to reach deeper layers of the gastrointestinal wall.AIM To investigate the utilisation,safety and diagnostic yield of an intensified“biteon-bite”tunnel biopsy technique.METHODS In this retrospective cohort study,all patients presenting with subepithelial masses in the upper gastrointestinal tract from March 2013 to July 2019 were included.Data were analysed for size and location of the subepithelial mass,use of intensified tunnel biopsy protocol(more than 10 double bite-on-bite biopsies)or superficial conventional biopsies,histology and imaging results,occurrence of readmission and adverse events after endoscopy.RESULTS Two hundred and twenty-nine patients with subepithelial lesions were included.Superficial conventional biopsies were taken in 117 patients and were diagnostic only in one lipoma(0.9%).Tunnel biopsies taken in 112/229(48.9%)patients were significantly more likely to provide histological diagnosis(53.6%;P<0.001).For lesions≥10mm the diagnostic yield of tunnel biopsies further increased to 41/67(61.2%).No immediate or delayed complications were reported.Only 8 of the 51 endoscopists(15.7%)regularly attempted tunnel biopsies.CONCLUSION Tunnel biopsy is a simple,safe and efficient but underutilised diagnostic modality for tissue acquisition in subepithelial masses.It should be routinely attempted at the initial endoscopy.

Role of molecular analysis in the adjuvant treatment of gastrointestinal stromal tumours: It is time to define it

Sendur et al pointed out the attention on the importance of mutational analysis for adjuvant treatment of gastrointestinal stromal tumor (GIST) in an article published in World Journal of Gastroenterology . In particular, they suggested that the optimal dose and duration of adjuvant therapy could be defined by the mutational status of the primary disease. This comment would underline the importance of centralised laboratories, given the increasingly important role of molecular analysis in the work-flow of all GIST, and the need of retrospective analyses for subgroups population stratified for the mutational status from the available studies in the adjuvant setting, in order to define the role of mutational analysis in choosing the optimal dose and duration of adjuvant therapy.

Differential diagnosis of diarrhoea in patients with neuroendocrine tumours: A systematic review

BACKGROUND Approximately 20%of patients with neuroendocrine tumours(NETs)develop carcinoid syndrome(CS),characterised by flushing and diarrhoea.Somatostatin analogues or telotristat can be used to control symptoms of CS through inhibition of serotonin secretion.Although CS is often the cause of diarrhoea among patients with gastroenteropancreatic NETs(GEP-NETs),other causes to consider include pancreatic enzyme insufficiency(PEI),bile acid malabsorption and small intestinal bacterial overgrowth.If other causes of diarrhoea unrelated to serotonin secretion are mistaken for CS diarrhoea,these treatments may be ineffective against the diarrhoea,risking detrimental effects to patient quality of life.AIM To identify and synthesise qualitative and quantitative evidence relating to the differential diagnosis of diarrhoea in patients with GEP-NETs.METHODS Electronic databases(MEDLINE,Embase and the Cochrane Library)were searched from inception to September 12,2018 using terms for NETs and diarrhoea.Congresses,systematic literature review bibliographies and included articles were also hand-searched.Any study designs and publication types were eligible for inclusion if relevant data on a cause(s)of diarrhoea in patients with GEP-NETs were reported.Studies were screened by two independent reviewers at abstract and full-text stages.Framework synthesis was adapted to synthesise quantitative and qualitative data.The definition of qualitative data was expanded to include all textual data in any section of relevant publications.RESULTS Forty-seven publications(44 studies)were included,comprising a variety of publication types,including observational studies,reviews,guidelines,case reports,interventional studies,and opinion pieces.Most reported on PEI on/after treatment with somatostatin analogs;9.5%-84%of patients with GEP-NETs had experienced steatorrhoea or confirmed PEI.Where reported,14.3%–50.7%of patients received pancreatic enzyme replacement therapy.Other causes of diarrhoea reported in patients with GEP-NETs included bile acid malabsorption(80%),small intestinal bacterial overgrowth(23.6%-62%),colitis(20%)and infection(7.1%).Diagnostic approaches included faecal elastase,breath tests,tauroselcholic(selenium-75)acid(SeHCAT)scan and stool culture,although evidence on the effectiveness or diagnostic accuracy of these approaches was limited.Assessment of patient history or diarrhoea characteristics was also reported as initial approaches for investigation.From the identified evidence,if diarrhoea is assumed to be CS diarrhoea,consequences include uncontrolled diarrhoea,malnutrition,and perceived ineffectiveness of CS treatment.Approaches for facilitating differential diagnosis of diarrhoea include improving patient and clinician awareness of non-CS causes and involvement of a multidisciplinary clinical team,including gastroenterologists.CONCLUSION Diarrhoea in GEP-NETs can be multifactorial with misdiagnosis leading to delayed patient recovery and inefficient resource use.This systematic literature review highlights gaps for further research on prevalence of non-CS diarrhoea and suitability of diagnostic approaches,to determine an effective algorithm for differential diagnosis of GEP-NET diarrhoea.

CLINICAL EFFECTIVENESS OF ELECTRO-ACUPUNCTURE THERAPY IN TREATING MAXILLOFACIAL TUMOURS

Electrochemical therapy, ECT, has been used to treat 122 cases of various kinds of tu-mour, among them, 81 cases were malignant tumours (32 cases facial, 18 cases subaural, 16 cases labial, 15 cases tongue), and the other 41 cases were bening tumours (cavermous hemangioma at facial region 23 cases and in oral cavity 18 cases). Pathological examination of malignant tumours revealed that there were 63 cases of squamous epithelial cancers and 18 cases of adenocarcinoma. Cavermous he-mangioma is benign tumour and congenital. Special designed and made platinum needles were inserted into the tumours and the needles were connected to an instrument protucing a direct current for treat-ment. Voltage used was usually 8 volts with current 60 - 80 mA. The quantity elecricity applied was 100 coulombs per 1 cm in diameter of the tumour. The effectiveness of treating 81 cases malignant tu-mours was: CR 42 cases (51. 8% ), PR 31 cases (38. 3% ), NC 5 cases (6. 2% ) and PD 3 cases (3.7 % ). CR + PR was 73 cases (90. 1 % ). The effectiveness of treating 41 cases of benign hemangioma was: CR 38 cases (92. 7 % ) and PR 3 cases (7. 3 % ). One, three and five year survival rates of malig-nant tumour patients were 95 %, 65. 4 % and 37 %, respectively. While all the 41 patients with he-mangioma survived over five years after treatment.

Time to give up traditional methods for the management of gastrointestinal neuroendocrine tumours

Neuroendocrine tumors(NETs)are a rare and heterogeneous disease group and constitute 0.5%of all malignancies.The annual incidence of NETs is increasing worldwide.The reason for the increase in the incidence of NETs is the detection of benign lesions,incidental detection due to the highest use of endoscopic and imaging procedures,and higher recognition rates of pathologists.There have been exciting developments regarding NET biology in recent years.Among these,first of all,somatostatin receptors and downstream pathways in neuroendocrine cells have been found to be important regulatory mechanisms for protein synthesis,hormone secretion,and proliferation.Subsequently,activation of the mammalian target of rapamycin pathway was found to be an important mechanism in angiogenesis and tumor survival and cell metabolism.Finally,the importance of proangiogenic factors(platelet-derived growth factor,vascular endothelial growth factor,fibroblastic growth factor,angiopoietin,and semaphorins)in the progression of NET has been determined.Using the combination of biomarkers and imaging methods allows early evaluation of the appropriateness of treatment and response to treatment.

Histidine decarboxylase and urinary methylimidazoleacetic acid in gastric neuroendocrine cells and tumours

AIM: To study histidine decarboxylase(HDC) expression in normal and neoplastic gastric neuroendocrine cells in relationship to the main histamine metabolite. METHODS: Control tissues from fundus(n = 3) and corpus(n = 3) mucosa of six patients undergoing operations for gastric adenocarcinoma, biopsy and/or gastric surgical specimens from 64 patients with primary gastric neuroendocrine tumours(GNETs), as well as metastases from 22 of these patients, were investigated using conventional immunohistochemistry and double immunofluorescence with commercial antibodies vs vesicular monoamine transporter 2(VMAT-2), HDC and ghrelin. The urinary excretion of the main histamine metabolite methylimidazoleacetic acid(U-Me Im AA) was determined using highperformance liquid chromatography in 27 of the 64 patients.RESULTS: In the gastric mucosa of the control tissues, co-localization studies identified neuroendocrine cells that showed immunoreactivity only to VMAT-2 and others with reactivity only to HDC. A third cellpopulation co-expressed both antigens. There was no co-expression of HDC and ghrelin. Similar results were obtained in the foci of neuroendocrine cell hyperplasia associated with chronic atrophic gastritis type A and also in the tumours. The relative incidence of the three aforementioned markers varied in the tumours that were examined using conventional immunohistochemistry. All of these GNETs revealed both VMAT-2 and HDC immunoreactivity, and their metastases showed an immunohistochemical pattern and frequency similar to that of their primary tumours. In four patients, increased U-Me Im AA excretion was detected, but only two of the patients exhibited related endocrine symptoms. CONCLUSION: Human enterochromaffin-like cells appear to partially co-express VMAT-2 and HDC. Coexpression of VMAT-2 and HDC might be required for increased histamine production in patients with GNETs.

Impact of tumour rupture risk on the oncological rationale for the surgical treatment choice of gastrointestinal stromal tumours

Tumour rupture of gastrointestinal stromal tumours(GISTs)has been considered to be a remarkable risk factor because of its unfavourable impact on the oncological outcome.Although tumour rupture has not yet been included in the current tumor-node-metastasis classification of GISTs as a prognostic factor,it may change the natural history of a low-risk GIST to a high-risk GIST.Originally,tumour rupture was defined as the spillage or fracture of a tumour into a body cavity,but recently,new definitions have been proposed.These definitions distinguished from the prognostic point of view between the major defects of tumour integrity,which are considered tumour rupture,and the minor defects of tumour integrity,which are not considered tumour rupture.Moreover,it has been demonstrated that the risk of disease recurrence in R1 patients is largely modulated by the presence of tumour rupture.Therefore,after excluding tumour rupture,R1 may not be an unfavourable prognostic factor for GISTs.Additionally,after the standard adjuvant treatment of imatinib for GIST with rupture,a high recurrence rate persists.This review highlights the prognostic value of tumour rupture in GISTs and emphasizes the need to carefully take into account and minimize the risk of tumour rupture when choosing surgical strategies for GISTs.